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Abstract: Colorectal cancer (CRC) is one of the leading causes of cancer death in humans. In order to identify novel cancer-promoting genes in CRC, we here constructed a retroviral cDNA expression library from a CRC cell line RKO, and used it for a focus formation assay with mouse 3T3 fibroblasts, leading to the identification of 42 independent cDNAs. One of such cDNAs turned out to encode purinergic receptor P2Y, G-protein coupled, 2 (P2RY2). The oncogenic potential of P2RY2 was confirmed in vitro with the focus formation assay as well as soft agar-growth assay, and also in vivo with a tumorigenicity assay in nude mice. While our P2RY2 cDNA encodes a protein with two amino-acid substitutions compared to the reported one, we have confirmed that the wild-type P2RY2 has a strong transforming potential as well. These results indicate an unexpected role of P2RY2 in the carcinogenesis of human cancers. [Copyright &y& Elsevier]

The article presents the case study of a 44-year-old man who underwent a double-balloon endoscopy (DBE) for hepatolithiasis with stones associated with reflux of intestinal contents to the bile duct due to Roux-en-Y hepaticojejunostomy. It says that at the age of 33-year old, he underwent choledochal cyst excision and hepatolithiasis with multiple stones was detected by abdominal computed tomography. It adds that the cholangioscopy demonstrated no residual stones and tumors.

Background: Little is known about the long-term results of endoscopic papillary balloon dilation (EPBD) for bile duct stones. Methods: Between 1995 and 2000, 204 patients with bile duct stones successfully underwent EPBD and stone removal. Complete stone clearance was confirmed using balloon cholangiography and intraductal ultrasonography (IDUS). Long-term outcomes of EPBD were investigated retrospectively in the year 2007, and risk factors for stone recurrence were multivariately analyzed. Results: Long-term information was available in 182 cases (89.2%), with a mean overall follow-up duration of 9.3 years. Late biliary complications occurred in 22 patients (12.1%), stone recurrence in 13 (7.1%), cholangitis in 10 (5.5%), cholecystitis in four, and gallstone pancreatitis in one. In 11 of 13 patients (84.6%), stone recurrence developed within 3 years after EPBD. All recurrent stones were bilirubinate. Multivariate analysis identified three risk factors for stone recurrence: dilated bile duct (>15 mm), previous cholecystectomy, and no confirmation of clean duct using IDUS. Conclusion: Approximately 7% of patients develop stone recurrence after EPBD; however, retreatment with endoscopic retrograde cholangiopancreatography is effective. Careful follow up is necessary in patients with dilated bile duct or previous cholecystectomy. IDUS is useful for reducing stone recurrence after EPBD. [ABSTRACT FROM AUTHOR]

When performing endoscopic retrograde cholangiopancreatography (ERCP), the smooth introduction of the duodenoscope into the papilla of Vater, an appropriate view of the papilla of Vater, and deep cannulation of the bile duct are essential. The operator must know the difference between the side-viewing endoscope and the forward-viewing endoscope. The rotation of the body and the left arm of the operator, switching with the left wrist, and dialing of the endoscope are essential for appropriately viewing the papilla of Vater. When training operators to do ERCP, a model is useful for helping them understand basic handling. The approach to deep cannulation of the bile duct should be selected based on the type of papilla (slit type, onion type, tongue protrusion type, flat type, and tumor type). Cannulation is more difficult in patients with the tongue protrusion-type of papilla than with a slit type, onion type, or tumor type. According to previous reports, therapeutic ERCP requires the ability to cannulate the common bile duct deeply 80% of the time; 180 to 200 supervised ERCP are necessary to achieve this success rate. [ABSTRACT FROM AUTHOR]

Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. Here we show that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells. Mouse 3T3 fibroblasts forced to express this human fusion tyrosine kinase generated transformed foci in culture and subcutaneous tumours in nude mice. The EML4–ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined; these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. Our data demonstrate that a subset of NSCLC patients may express a transforming fusion kinase that is a promising candidate for a therapeutic target as well as for a diagnostic molecular marker in NSCLC. [ABSTRACT FROM AUTHOR]

Biphenotypic acute leukemia (BAL) is a relatively rare subtype of acute leukemia characterized by the presence of both myeloid and lymphoid cell surface antigens. We have now screened for transforming genes in BAL blasts with the use of the focus formation assay with a retroviral cDNA expression library constructed from malignant blasts isolated from a BAL patient. Some of the retroviral inserts recovered from transformed foci were found to encode wild-type purinergic receptor P2Y, G protein coupled, 8 (P2RY8). The oncogenic potential of P2RY8 was confirmed with the in vitro focus formation assay as well as with an in vivo tumorigenicity assay in nude mice. A variety of luciferase-based reporter assays revealed that P2RY8 increased both the trans-activation activities of CREB and Elk-1 as well as the transcriptional activities of the serum response element and enhancer-promoter fragments of the c-Fos and c-Myc genes. Quantitation of P2RY8 mRNA in CD34+ cells of bone marrow showed that P2RY8 expression is frequently increased in leukemia patients, especially in those with refractory disease. Our data thus reveal an abundant expression of P2RY8 in leukemic cells and its unexpected role in the pathogenesis of acute leukemia. [ABSTRACT FROM AUTHOR]

Abstract: To identify transforming genes in acute myeloid leukemia (AML) we here constructed a retroviral cDNA expression library from an AML patient, and then used this library to infect a mouse cell line 32Dcl3-mCAT. cDNA inserts of the cell clones which proliferated in the presence of granulocyte colony-stimulating factor were derived from JAK3 encoding a JAK3 mutant with a valine-to-alanine substitution at codon 674 and two additional amino acid substitutions. The transforming activity of JAK3(V674A) was confirmed by its introduction into 32Dcl3-mCAT. Sequencing of the original JAK3 cDNA derived from the patient, however, failed to detect the V674A mutation. [Copyright &y& Elsevier]

The article presents information on the case of a 78-year-old man who was presented to hospital with epigastric pain. It has been concluded that gadolinium is a reasonable alternative to iodine-based endoscopic retrograde cholangiopancreatography (ERCP) contrast in patients with severe iodine allergy.